Lymphangioleiomyomatosis: The Lonely Disease

When Sue Byrnes found out that her 22-year-old daughter, Andrea, had pulmonary lymphangioleiomyomatosis (LAM), she could have sat back helplessly and waited for the fatal disease to kill her child. Instead she took action. First, she initiated the creation of a national registry listing people who had the rare disease, and, when that task was completed, she founded the LAM Foundation—which offers support to patients with the disease and money for research. The 6-year-old organization’s efforts have already borne fruit including a genetic breakthrough that may help researchers understand and eventually cure the disease.

The Lonely Disease

LAM has been nicknamed the “lonely disease.” First identified in 1937, it is characterized by the advancement of smooth muscle tissue into the lung, including the airways and lymph and blood vessels. This smooth muscle tissue, which acts like a cancer, although the cells are not cancerous, eventually forms into thick bundles causing the air, blood, and lymph pathways to become obstructed. In the early stages of the disease, the sufferer experiences shortness of breath associated with strenuous physical activity, and as the disease advances, patients have shortness of breath even at rest, requiring the use of supplemental oxygen. Collapsed lungs and blood clots are common. The disease is extremely rare with only about 375 identified patients in the United States and another 525 scattered throughout the world. The disease is almost exclusive to women (there is one documented case of a man with LAM) and strikes during their childbearing years; it seems to be accelerated by pregnancy. The disease does not act the same in every woman—Byrnes’ daughter, for instance, is symptom-free at the moment.

“[Many] women received medical attention because they were short of breath. In most studies, the survival is on the average of 10 years,” says Frank McCormack, MD, the director of the LAM Foundation’s scientific board and an associate professor of pulmonary and critical medicine at the University of Cincinnati. “But people discovered earlier in the disease process that those statistics don’t necessarily apply. In general, it progresses very slowly. It’s hard to measure change from year to year. Over several years, one can measure decline in lung function and an increased number of cysts on computed tomography scans. In some people it moves more quickly and we don’t understand [why].” There is no evidence that the disease is genetically inheritable.

Research

Byrnes, who was a teacher at the time of her daughter’s diagnosis, launched a letter-writing campaign with the help of the National Education Association to set up a national registry of LAM patients with the National Institutes of Health (NIH). The establishment of the registry did not mean it would attract research assistance, but Byrnes wanted to make a difference. She wanted to find a way to help her daughter, so she created the LAM Foundation. “Most people say ‘you have tremendous love for your daughter. You must have been terribly afraid of losing her,’” she says. “As painful as that is to think about, it’s not so much the thought of losing her but the fact that she wouldn’t have the opportunity to lead a full life—the one she deserves.”

Since its inception, which started in Byrnes’ Cincinnati home in 1995, the LAM Foundation has raised more than $2.5 million—of which $2.3 million has been used to do research on the disease. “[Research] is our central focus, which we believe is the most important thing we can do right now,” Byrnes says. “That doesn’t mean other things aren’t important too. Our Lamposium is extremely important to us, and we have been fortunate enough to get sponsorship for that. So we’ve been able to raise funds to support the conference so that it does not take money from research.”

It is in science that the LAM patients find the most hope, says Byrnes, adding that her greatest challenge has been creating interest in a disease that is virtually unknown to pulmonary specialists and researchers. But this problem exists only until the researchers are introduced to the disease. “Once scientists look at LAM, they find it to be a very intriguing disease,” she says. “[Attracting researchers] was our greatest challenge and now that’s one of the most exciting things we have going for us. We have been able to attract the interest of scientists from high-quality laboratories.”

McCormack says the researchers are attracted to LAM because it is an intrinsically interesting disease. “There are connections with TS (tuberous sclerosis) that make it interesting,” he says. “The fact that the lung becomes completely replaced by cysts is fascinating and how that happens is too.” McCormack reviews about four LAM research grants every 6 months. Currently, there are 30 ongoing research studies.

And the interest in research shown by the larger medical community concerning LAM includes the foundation’s alliance with the American Lung Association, Byrnes’ address to the National Institutes of Health in 2000, her appointment to the advisory council of the National Heart, Lung, and Blood Institute, and the foundation’s yearly Lamposium in Cincinnati.

The 3-day symposium, which was held on March 30-April 1, attracted a wide range of researchers and physicians to discuss such topics as “Pathology in LAM,” “Molecular Basis of TSC [tuberous sclerosis complex],” “Pregnancy and LAM,” and “Adverse Effects of Hormonal Therapy in LAM Patients.” What makes Lamposium different from other medical symposia is that the patients who attend are able to meet and interact with the researchers. “When the scientists meet the patients, it has a tremendous impact on them,” Byrnes says. “They tell us it makes them more determined to find answers because they’re touched by the women with LAM and even more touched by their positive attitudes. We think that’s one of the most valuable things we do—getting the researchers and the patients together.”

Genetic Breakthrough

It was a LAM Foundation-funded researcher who made the genetic breakthrough last year—one that may help researchers understand this “lonely” disease on a broader scale. “I think ‘breakthrough’ is the appropriate term because this finding links sporadic LAM—LAM that occurs in patients without TS—to LAM that occurs in patients with TS,” McCormack says. “And that’s very important because it gives us the advantage of having a very well-developed TS research field, investigating questions that are important to LAM as well. Not only were the same genes involved in sporadic LAM as are involved in TS, but there is genetic evidence that the disease may be a metastatic process. Patients with LAM frequently have either kidney tumors called angiomyolipomas or lymph node enlargement. If you look at the mutations that occur in the kidney tumors, you can find the same mutations in the lung tissue that is diseased with LAM; however, they are not found anywhere else in the body—just identical mutations that are present in the kidney tumor and lesional lung tissue. That suggests at least the possibility of a tumor forming in the kidney because of a mutational event, and then the cells migrate from the kidney to the lung (that’s speculation) but it creates a new model for LAM that has us thinking about the disease in a different way.”

Providing Support

Although research is the primary mission of the foundation, so is support. “We are just like family,” says Byrnes, who has personally called almost every LAM patient on the foundation’s rolls. “The efforts have expanded beyond what has been done for my daughter. Now that I’ve gotten to know and love all these other LAM patients, the efforts are there for them as well because they are tremendous women.” The foundation supports them with a patient directory, newsletter, Internet listserv, yearbook, videos, and teleconferences.

Because the disease is always fatal, Byrnes has lost members of her LAM family. “It’s devastating when I hear of another LAM patient dying,” she says. “At the same time, you can’t let it get you down. It gives you more reason to be determined and move forward to make sure you don’t lose one more woman.”

Since the disease progresses slowly, there are things patients can do to manage it. Because childbearing seems to accelerate the progression of LAM, many doctors prescribe progesterone and recommend their patients not have children. Pulmonary rehabilitation, which includes graded exercise and walking, has been effective for many patients in the early stages of the disease. As the disease blocks their airways, patients begin using supplemental oxygen. In the last stages of the disease, the treatment option is a lung transplant—a “last resort” treatment that has proven to be effective, Byrnes says.

Apart from getting more scientists involved in researching the disease, Byrnes is working to identify more women who have LAM because the rareness of the disease means it is frequently misdiagnosed. As part of this effort, she has sent out a letter to 7,000 pulmonologists and is a regular attendee at medical and women’s conferences. At a recent conference, she helped to identify three women who had LAM.

The genetic breakthrough has given the LAM Foundation a focus, Byrnes says. For McCormack, it has raised his optimism. “I think there are clues that make me optimistic that we’re going to find answers to help patients in this generation,” he says.

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Chris Wolski is associate editor of RT Magazine.